Fig. 7
From: Activated cofilin exacerbates tau pathology by impairing tau-mediated microtubule dynamics
Cofilin activity is required for synaptic dysfunction and tau pathology in Tau-P301S mice. a, b Hippocampal primary neurons derived from WT, Tau-P301S, and Tau-P301S;cofilin+/− were transduced with mRFP, cofilin-S3A-mRFP, or cofilin-S3E-mRFP adenovirus on DIV7 and subjected to immunocytochemistry for synaptophysin on DIV21 (scale bar = 20 μm). White rectangular box areas of synaptophysin staining magnified in lower panels. b Quantification of synaptophysin intensity in primary neurites. Data are expressed as mean ± SEM (one-way ANOVA with Tukey post hoc, n = 15–20/genotype, #p < 0.0001 compared to WT mRFP control). c, d Three-month-old WT, Tau-P301S, and Tau-P301S;cofilin+/− mice transduced with purified high-titer mRFP rAAV9 or cofilin-mRFP variants (S3A or S3E) rAAV9 by stereotaxic injection into the hippocampus. Brain tissues 3 months post-transduction were processed for direct confocal microscopy for mRFP and cofilin-mRFP variants as well as indirect immunohistochemistry for synaptophysin (scale bar = 100 μm). d Quantification of synaptophysin intensity performed from the stratum lucidum (SL) of CA3. Data are expressed as mean ± SEM (one-way ANOVA with Tukey post hoc, 4 mice/genotype, ***p = 0.0006, #p < 0.0001 compared to WT mRFP control). e, f Three-month-old WT, Tau-P301S, and Tau-P301S;cofilin+/− mice transduced with purified high-titer mRFP rAAV9 or cofilin-mRFP variants (S3A or S3E) rAAV9 by stereotaxic injection into the hippocampus. Brain tissues 3 months post-transduction were processed for direct confocal microscopy for mRFP and cofilin-mRFP variants as well as indirect immunohistochemistry for tau-pS199/pS202 (scale bar = 20 μm). f Quantification of tau-pS199/pS202 intensity in transduced neurons. Data are expressed as mean ± SEM (one-way ANOVA with Tukey post hoc, 4 mice/genotype, #p < 0.0001 compared to P301S mRFP control)
